1. Determination of the Optic Disc Cupping in Glaucoma
Syed S. Hasnain M.D.
560 W. Putman Ave # 6
Porterville CA 93257, U.S.A.
test
Author has no financial interest in this presentation.

2. Purpose
The term cupping implies that the physiological cup begins enlarging in glaucoma.
The terms cupping and simple glaucoma have been synonymous since the 1850’s.
This presentation is to determine whether or not cupping is occurring. If it is not cupping, then what may be occurring to the physiological cup?
The methods section discusses three puzzling questions and how their answers by deductive reasoning and photographic evidence led to the conclusion that the optic disc may not be cupping, but instead sinking in its entirety.

3. Methods: Three Puzzling Questions in Glaucoma
Question 1: Why do some patients develop glaucoma at a normal IOP such as 15mmHg, while others do not at a high IOP such as 30mmHg?
Question 2: Why are the arcuate fibers selectively destroyed first, whereas the macular fibers last until the end stage of glaucoma?
Question 3: Why can’t we halt glaucoma in spite of maximally lowering of IOP with treatment?
We have no satisfactory answer for the above puzzling questions. I would try to answer these questions.
Answers to the above questions are discussed in this presentation.

4. Discussion: Puzzling Question #1 Why do some patients develop glaucoma at a normal IOP such as 15mmHg (NTG), while others don’t at a high IOP such as 30mmHg (Ocular Hypertension)?
Medical history revealed that HTG patients were usually in good health, whereas the NTG patients had cardio-pulmonary and circulatory problems. Furthermore, about 70% of NTG patients were smokers.
Findings suggest that NTG may be a systemic disease and glaucoma a multifactorial disease. Glaucoma being a multifactorial disease may be the answer to question # 1. More the risk factors present, higher the likelihood of development of glaucoma.
This raises another question: If HTG is an ocular disease, whereas NTG a systemic disease, then why are the arcuate field defects present in both cases? If glaucoma is a multifactorial disease, then there should be a common site of injury somewhere in the course of pathogenesis of both HTG and NTG.
Since arcuate fibers are destroyed in both HTG and NTG, the pursuit of their pathogenesis may lead to a common site of injury.
This is my answer to my first Q. Why some do some develop glaucoma At normal IOP of 15 and others not at 30. because glaucoma is a multifactorial disease.

5. Discussion: Puzzling Question # 2 Can the arcuate fibers in the disc or in retina be selectively destroyed by any pathology ?
Not likely. How is it possible that high IOP, or any other pathology, can selectively and precisely destroy only the arcuate fibers among the one million or so densely packed nerve fibers in the optic disc? If this is not possible, then the optic disc may not be the primary site of injury.
How is it possible that high IOP, or any other pathology, can selectively and precisely destroy only the arcuate fibers of the retina? If this is not possible, then the retina may not be the primary site of injury.
Regarding apoptosis: How is it possible that apoptosis in glaucoma will initiate selectively with only those ganglion cells
of retina which serve the arcuate fibers? If this is not possible, then apoptosis of the ganglion cells may not be occurring.
If the disc or retina is not the primary site of injury, then what may be the primary site of injury? We are left with the circular border tissue which we will discuss in next slide.

6. Discussion: Can the border tissue be the common site of injury?
Circular border tissue lies between the optic disc and scleral rim and secures the disc in the scleral opening.
Border tissue is exclusively supplied by short posterior ciliary arteries (ciliary circulation). Ciliary circulation is a low pressure system due to its multiple branches as compared to the CRA which mainly remains solitary from its origin.
IOP and arterial pressure are opposing forces.
Normally, IOP should be lower than the arterial pressure of the border tissue for its healthy maintenance.
The above circulatory balance would be reversed due to either an increase in IOP or decrease in arterial pressure resulting from poor systemic circulation. In the latter scenario, even normal IOP would become high for that particular eye and would compress the already weak circulation of the border tissue. This would result in chronic ischemia and atrophy of border tissue and thus sinking of optic disc.
SPCS’S has lower pressure system due to its multiple branches whereas CRA is higher pressure since it remains solitary from its origin from ophthalmic.

7. Discussion: Can the arcuate fibers be selectively destroyed if optic disc is sinking?
Likely. As the border tissue atrophies, the optic disc would become loose and begin to sink.
Since the optic disc usually has an oblique entry in the globe, the temporal part is more closer to the scleral edge (rim).
As the disc sinks, all temporal fibers (superior, inferior arcuate, and macular) would be stretched and severed at the scleral rim. However, since the arcuate fibers are fewer in number, they would be depleted earlier, giving rise to double arcuate field defects, whereas the macular fibers being abundant would last until the end stage of glaucoma. This may be the answer to question #2: that why are the arcuate fibers selectively destroyed?

8. Results: Optic disc may be sinking as it can explain the production of arcuate field defects
Temporal sinking would result in severing of the macular and sup.& inf. arcuate fibers. However since arcuate fibers (blue) are fewer in number they would be depleted earlier, giving rise to double arcuate field defects whereas the macular fibers being abundant would last until the end-stage.
Double arcuate field defect
on perimetry

9. Early and Late Stage Glaucomatous Discs Patients A & B
Late stage left eye of same patient A: Physiological cup is broken due to confluence of cup pallor with the pallor produced by the destruction of nerve fibers in the peripheral part. Marked kinking of blood vessels at disc margin due to loss of underneath nerve fibers.
Patient A: Early stage Right eye: No change in contour of the physiological cup. Prominent scleral edge due to thinning of RNFL from severing and depletion. Sloping of blood vessels due to sinking disc. splinter hemorrhage at 7o’clock due to severing of smaller blood vessel.
Patient B: Early stage Right eye: No change in the contour of
physiological cup. Prominent scleral edge due to thinning of RNFL. Sloping of blood vessels due to sinking of disc.
Late stage left eye of same patient B. Physiological cup is obliterated. Marked kinking of blood vessels at disc margin due to loss of underneath nerve fibers. Pa

10. Analogy: Sinking manhole cover to a glaucomatous disc
Normal: Manhole cover flush with the road. Blood vessels are straight at the margin of the disc. If there is no sloping or kinking of blood vessel at the margin, then there is no sinking of the disc and probably no glaucoma.
Early stage glaucoma: Physiological cup is still intact. Splinter hemorrhage at 7 o’clock. Kinking and sloping of the blood vessels. Arcuate field defect present. Temporal part pale and sunken due to thinning of RNFL.
Late stage glaucoma: Physiological cup is broken due to
confluence of cup pallor with pallor produced by the
destruction of nerve fibers in the peripheral part. Nasal
shifting of vessels from loss of anchorage due to earlier
thinning of temporal RNFL as compared to that of nasal RNFL.
End stage glaucoma: Total loss of the optic disc due to axotomy of the axons. Disc area becomes an empty crater. Only the larger blood vessels remain.

11. What happens as the sinking of the disc continues?
360 degrees of retinal nerve fibers anchor the optic disc in place as roots anchor a tree.
As the nerve fibers are being severed and depleted, the optic disc would become more loose and sinks further, resulting in severing of more nerve fibers. This is revealed by OCT – progressive thinning of the RNFL.
Severing of the nerve fibers creates a self-propagating cascade of loosening and sinking of the disc which would continue until all the nerve fibers are severed at the edge. This may be the answer to question # 3: that once glaucoma is initiated it cannot be halted.
At the end-stage, unlike any other disease, there is no optic disc and no nerve fibers. This is revealed by the histology of the end-stage glaucomatous disc – an empty crater.
Self propagating cascade reactions occurring in glaucoma is my answer to the last Q. Why can’t we halt the disease in spite of the maximum lowering of the IOP. Why we call 100% cupped disc when optic disc is not there anymore?

12. Conclusion:
Physiological cup may not be enlarging but breaking up (obliterating). Cupping occurring concentrically can’t explain arcuate field defects.
Fibers for the central vision are located in the central part of the disc and superficial (closer to the vitreous). Therefore, if cupping were occurring, then the central fibers should have been destroyed first but this is not the case because the central vision fibers are destroyed last in glaucoma.
In sinking, the peripheral fibers would be severed first because they lie deeper in close proximity to the scleral rim, whereas the central and superficial fibers last - this is what is occurring as revealed in glaucomatous field defects.
Continuous severing of prelaminer fibers due to continuous sinking of disc would result in progressive thinning of the RNFL– this is what revealed by OCT.
At the end-stage, the disc area is replaced with an empty crater due to severance (axotomy) of all the axons of the optic disc – this is what revealed by end-stage histology.